Líffræðifélag Íslands - biologia.is
Líffræðiráðstefnan 2023
Höfundar / Authors: Valgerður J. Hjaltalín (1), Margrét Helga Ögmundsdóttir (1)
Starfsvettvangur / Affiliations: 1. Háskóli Íslands
Kynnir / Presenter: Valgerður J. Hjaltalín
Autophagy is a highly conserved degradation pathway important for maintaining homeostasis in eukaryotic cells. The E1-like enzyme ATG7 belongs to a group of ATG proteins that mediate the autophagy process. Several autophagy independent functions of ATG7 have been described in mammalian models. We set out to investigate the evolutionary history of ATG7. We wanted to know whether a new functional region had emerged that could harbor a novel function. The study revealed a region of ATG7 that emerged early in vertebrates. Interestingly, this vertebrate specific region (VSR) is situated within the highly conserved active domain of the protein. Structural models of ATG7 predict that the VSR forms an intrinsically disordered loop that extends out from the protein. Experiments in MEFs expressing ATG7 lacking the VSR showed that they were unable to carry out its characterized function in autophagy. The role of the VSR remains to be fully elucidated, but two residues within the region have been linked to cancer in humans. To address these putative differences between vertebrates and invertebrates and possible effects on cancer progression, we have generated Drosophila melanogaster with Atg7 knockout and rescue with human ATG7. Unlike mammals, fruit flies are viable without Atg7, although they have a shorter lifespan and less tolerance to stress. Substitution with the human proteins partially rescued the phenotype and, in addition, produced a surprising additional phenotype.